The mammalian brain contains antigenic proteins which are specific to the nervous system. Little is known of the cellular localization of these proteins with the exception of protein S-100 which is usually considered of glial origin. A new brain specific protein, different from protein S-100 in amino acid composition, molecular weight, solubility and electrophoretic mobility has been recently isolated in our laboratory from severely gliosed human brain tissue and, more recently, from normal human brain. Since the protein is a major component of tissues which are predominantly formed of glial fibers, and because it contains high proportions of dicarboxylic amino acids, it was called the glial fibrillary acidic protein (GFAP). Using antibodies against the GFAP astrocytes are selectively stained by immunofluorescence in man and many vertebrate species. By immunodiffusion and immunoelectrophoresis cross reacting with human GFAP antiserum is present in many vertebrates, including the dogfish. We propose to study: a) human GFAP from normal gray and white matter at different ages and in various pathological conditions; b) the distribution of GFAP in subcellular fractions and the localization of GFAP at the EM level using peroxidase coupled antibodies. If the GFAP is related to glial filaments dissociation and reconstitution experiments will be attempted with isolated filaments and purified GFAP; c) the differentiation of astrocytes in pre- and postnatal development as assessed by the time of appearance of GFAP: d) astrocytic development in Quaking and Reeler mice. (We have shown that in the rat pyramidal tracts astrocytes differentiate at the time of myelination gliosis, and that in the rat cerebellum Bergmann fibers appear before neuronal migration from the external granular layer and attain their mature shape at the time of neuronal migration from this layer); e) as assessed by the production of GFAP: the development of fibrous gliosis in Wallerian degeneration of the optic nerves and in infant rats at high altitude; astrocytic differentiation in organotypic cultures of CNS tumors; Alzheimer type II astrocytes in porto-caval anastomosis; f) anti-GFAP antibodies and GFAP in serum and CSF of patients with neurological disease; g) the effects of anti-GFAP antibodies on brains and CNS explants; and h) GFAP in philogenesis.